Search PubMed⌕ Search

Biomedical subjects

I D Watson

Publications and source records attributed to I D Watson.

At least 73 records · Page 4Linked to original sources
PubMed1986

Trimethoprim: prediction of serum concentrations from saliva measurements.

Saliva has been used in the past as a non-invasive predictor of serum drug concentration. Prediction may be made from a regression line of saliva versus serum concentration or from an equation proposed by Matin et al. (1974); such predictions have been examined for trimethoprim, a drug that has a pKa of 7.3, the degree of ionisation influencing its partition between saliva and serum. A relationship was found between serum and saliva trimethoprim concentrations. Salivary trimethoprim concentrations were marginally related to salivary flow rate, but not salivary pH. The precision and bias of prediction from linear regression and the equation of Matin et al. (1974) was considered; the equation did not describe the relationship between serum and saliva trimethoprim concentrations and we conclude that its use is inappropriate.

Adult↗
PubMed1986

Fatal xylenol self-poisoning.

A case of fatal xylenol ingestion by a long-stay mental hospital patient is described. The clinical course was similar to that observed in other phenolic poisonings with active bowel sounds, nausea and vomiting, severe metabolic acidosis, hypotension and cardiac and renal failure. The formulation of xylenol ingested contains alcohol which would facilitate absorption; due to the dangers of such poisonings care must be exercised as to access and exposure to xylenol sterilising agents.

Disinfectants↗
PubMed1986

Micro-scale ultracentrifugation as an alternative to ultrafiltration for the determination of the unbound fraction of phenytoin in human serum.

Free phenytoin has been determined using micro-scale ultracentrifugation followed by analysis by EMIT. The effect of temperature on the determined free fraction was investigated and the ultracentrifugation procedure validated against ultrafiltration. Ultracentrifugation gave free fractions which were on average 16% lower than those obtained using ultrafiltration, but correlation was good, as was the correlation with measurements of total phenytoin (r = 0.90). Micro-scale ultracentrifugation is a simple procedure which can be of great utility in the measurement and investigation of free drug levels.

Blood Proteins↗
PubMed1985

Clavulanate-potentiated ticarcillin: high-performance liquid chromatographic assays for clavulanic acid and ticarcillin isomers in serum and urine.

High-performance liquid chromatographic assays for the determination of clavulanic acid and ticarcillin in biological fluids are described. The clavulanic acid assay uses serum ultrafiltrate and direct injection of diluted urine with reversed-phase ion-pair/counter-ion chromatography. The ticarcillin assay allows, for the first time, the separation and quantitation of two isomers of ticarcillin. The performance of these assays has been evaluated and found to be satisfactory for routine clinical use and thus the assays have been applied to the study of the pharmacokinetics of these analytes in a subject with renal failure.

Anti-Bacterial Agents↗
PubMed1985

Comparison of serum and cerebrospinal fluid levels of methotrexate in man during high-dose chemotherapy for aggressive non-Hodgkin's lymphoma.

The relationship between plasma and cerebrospinal fluid levels of methotrexate was studied in five patients, four with aggressive non-Hodgkin's lymphoma and one with mixed epithelial mesothelial tumour, who were treated with high-dose methotrexate (1.5 g/m2) as part of combination chemotherapy. Cerebrospinal fluid was sampled for 24 h via a permanent indwelling lumbar catheter. No complications were observed with this technique. In two patients with central nervous system involvement adequate "cytotoxic" levels (greater than 10(-6) M) were obtained for greater than 12 h. The remaining three patients, with no direct evidence of central nervous system involvement, never attained adequate cytotoxic methotrexate levels in the cerebrospinal fluid. Serum levels were therapeutic in all patients. These results suggest that patients with central nervous system tumour involvement may receive adequate doses of methotrexate in the cerebrospinal fluid. Patients with occult central nervous system tumour involvement may not attain adequate cerebrospinal fluid levels. A 24-h serum methotrexate level of greater than 10(-5) M may indicate that patients have achieved therapeutic cerebrospinal fluid levels of methotrexate. Cranial irradiation following chemotherapy is still recommended in this tumour group until adequate cytotoxic levels of methotrexate can be obtained in all patients for prolonged periods.

Adult↗
PubMed1985

The effect of surfactants on the high-performance liquid chromatography of anthracyclines.

A rapid, reversed-phase high-performance liquid chromatographic method is described for the determination of the antineoplastic drug, doxorubicin (Adriamycin), and its major metabolites in plasma. The addition of anionic, cationic or non-ionic surfactants was found to reduce k'; the mechanisms of this finding are discussed and the performance of an optimized method using a non-ionic surfactant, Brij-35, is described for plasma samples.

Journal Article↗
PubMed1983

An assay for methotrexate and its metabolites in serum and urine by ion-pair high-performance liquid chromatography.

A high-performance liquid chromatographic assay for methotrexate and its metabolites, 7-hydroxy-methotrexate, 4-amino-4-deoxy-N10-methyl-pteroic acid and 7-hydroxy-4-amino-4-deoxy-N10-methyl-pteroic acid in the range 10 microg/l to 50 mg/l (2.2 x 10(-8) to 1.1. x 10(-4)M) has been developed using L-tryptophyl-L-glutamic acid as internal standard. Extraction was performed using an anion exchange resin (Dowex 1-X2) with subsequent ion-pair chromatography of the appropriate eluent fraction. The method has been found to be sensitive and precise for the analysis of both serum and urine, and may also be used for the quantitation of polyglutamyl metabolites.

Journal Article↗
PubMed1983

Pharmacokinetics of two dosage levels of trimethoprim to 'steady-state' in normal volunteers.

Trimethoprim (TMP), previously available only with a sulphonamide, is now available alone. The kinetics of two dosage regimens (200 mg b.d. p o. and 300 mg o.d. p.o.) have been examined. The expected disposition of higher TMP concentrations following the initial dose of the 300 mg preparation is reversed when steady-state is reached, and is a function of dosage. The MIC of TMP for sensitive organisms in urine was greatly exceeded following both regimens and is the result of a favourable pH gradient. The serum concentrations at CSS (trough) following the 300 mg regimen did not consistently exceed the MIC for TMP, those for the 200 mg regimen were more satisfactory. The implications of these findings are that while both regimens would be satisfactory in the treatment of urinary tract infection the 200 mg regimen would be more appropriate for the treatment of infected sites where pH dependent accumulation of TMP does not occur.

Adult↗
PubMed1981

Synergism between trimethoprim and sulfonamide in urine: does it exist?

In a randomized, crossover, multiple dose study, ten healthy volunteers received the recommended dosages of cotrimoxazole (80 mg trimethoprim and 400 mg sulfamethoxazole) and co-tri-famole (80 mg trimethoprim and 400 mg sulfamoxole) for five days each. Urinary levels of trimethoprim and each sulfonamide were measured daily for five days. The urinary ratios of trimethoprim and sulfonamide for both formulations were consistently lower than those considered optimal for synergy. Concentration of trimethoprim in the urine from both preparations was found to be greatly in excess of the MIC for trimethoprim-sensitive urinary pathogens (approximately 2 microgram/ml). The sulfonamide levels achieved were not consistently in excess of their MIC (approximately 200 microgram/ml) for either preparation.

Drug Combinations↗